This is an application for renewal of the Bay Area Breast Cancer Translational Research Program, a collaborative effort between the University of California, San Francisco (UCSF), and the California Pacific Medical Center (CPMC). The main themes of this SPORE are: * Developing therapies targeted at surface proteins uniquely expressed or overexpressed on breast cancer cells. * Identifying genetic abnormalities associated with progression of breast cancer from a precancerous condition to a state of unregulated growth, from in situ expansion to invasive and metastatic behavior, and from a drug sensitive to a drug resistant phenotype. * Developing therapies designed to inhibit enzymes of critical importance in the early stages of breast cancer cell invasion. * Constructing gene therapies that target membrane proteins and carry genes into the cancer cell that will either make it more sensitive to toxins or make a target of the host immune response. * Evaluating the extent to which possible targets of therapy are associated with the prognosis or response to therapy of patients with breast cancer. * Identifying women at high risk of developing breast cancer and discovering new approaches to preventing cancer in these high risk women. The research program will draw on outstanding molecular biology programs of UCSF, the breast cancer research program on prognostic factors currently funded by a PO-1 at CPMC, the newly developed multidisciplinary breast clinic at the UCSF cancer center, and the extensive clinical programs associated with the Breast Health Center at CPMC. The applications consists of four principal research projects, two developing projects, approximately 5 pilot projects per year, seven cores, and support for the career development of two new faculty members committed to breast cancer research. The principal research projects are: #1 "The development of membrane receptor targeted and tumoricidal breast cancer therapy." #2 "DNA sequence copy number abnormalities in human breast cancer." #3 "Molecular markers defining groups of women at unusually high risk of developing cancer." #4 "Therapeutic blockade of urokinase in breast cancer." "The proposal includes two new developing projects: "Ligand mediated targeting of retrovirus to breast cancer," and "Genomic instability in carcinogenesis of the breast." Two new cores are described: an immunohistopathology core and an advocacy core. Cores previously part of this SPORE include: #1 Administration; #2 Human fresh tissue bank; #3 An animal facility ; #4 Epidemiology and biostatistics; #6 Clinical core.